EMC10-Related Neurodevelopmental Disorder

Excerpt

Clinical characteristics: EMC10-related neurodevelopmental disorder (EMC10-NDD) is characterized by moderate-to-severe developmental delay and mild-to-severe intellectual disability. Seizures, speech delay, poor weight gain, and growth deficiency are common in individuals with EMC10-NDD. Neurobehavioral manifestations, microcephaly, kidney and urinary tract abnormalities (nephrocalcinosis, renal cysts, and hydronephrosis), and upper limb anomalies (cubitus valgus, arachnodactyly, and bilateral fifth digit clinodactyly) have been reported in a few individuals.

Diagnosis/testing: The diagnosis of EMC10-NDD is established in a proband by identification of biallelic pathogenic variants in EMC10 on molecular genetic testing.

Management: Treatment of manifestations: Developmental and educational support; standard treatments for behavioral manifestations, epilepsy, and renal manifestations; nutritional support for poor weight gain; social work and family support as needed.

Surveillance: Assessment of developmental progress and educational needs, musculoskeletal manifestations, behavioral issues, new seizures or changes in seizures, growth, nutrition, and family needs at each visit. Follow-up labs and imaging for kidney function, nephrocalcinosis, and renal cysts as recommended by nephrologist.

Genetic counseling: EMC10-NDD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an EMC10 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the EMC10 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.